The technique of intrinsic signal optical imaging of neural activity has been adapted to the noninvasive functional imaging of retina. Preliminary results demonstrate the feasibility and potential of this new method of functional assessment of the retina. However the technique is in its infancy and many issues must be resolved to provide a solid foundation for basic science and clinical applications. One major unanswered question concerns the sources and nature of the activity-dependent intrinsic optical signals in the retina, their properties and anatomic origins. This project proposes to conduct studies to address this issue along with the continued development and validation of the technique to yield a new tool for basic research and clinical applications in the retina. Towards this end, the primary goals of the proposed research plan are: - To improve the performance and optimize the protocol of the retinal functional imager. By careful selection of methodological parameters, such as wavelength and timing of the measurement and spatio-temporal properties of the visual stimulus, the performance of the retinal optical imaging protocol will be optimized. - To determine the conditions to isolate specific functional signals, to help reveal the underlying signal sources and anatomic origins. Similar tuning of parameters will also be aimed at revealing the various sources and origins of the signals that are imaged. This information will strongly impact the range of clinical applications that this technique would find applicability. -To characterize the spatial and contrast sensitivity properties of the signals. Basic measurements of the properties of spatial summation, contrast sensitivity, signal resolution and point spread image will additionally help determine the origins of the optical signals and lay the foundation for future basic science work. We have assembled a team representing expertise in functional optical imaging, biomedical image acquisition and processing, as well as research-oriented ophthalmologists, poised to translate the strong potential of this novel technique into practice. In sum, the proposed studies are designed to complete the adaptation of intrinsic signal optical imaging methods to the noninvasive functional assessment of retina and lay the groundwork for future basic science and clinical applications of this novel biomedical functional imaging technique.